Behavioral studies in human infants and neonatal rodents have demonstrated potent analgesic and claming effects triggered by mother's milk during nursing. This gustatory or taste analgesia is triggered by sugar and fatty constituents of mother's milk and is readily elicited in human and rat neonates by intraoral infusion of microliter quantities of mother's milk and sweet components of milk (sucrose, fructose, glucose). Taste analgesia is opiate receptor dependent. In rats, taste analgesia is blocked by systemic injection of opiate receptor antagonists, and taste analgesia is absent in human infants born of opioid-dependent mothers. Taste analgesia is clinically significant as sweet stimuli (e.g., sugar-coated pacifiers) are currently used to manage pain and stress produced by painful clinical procedures. However, the neural circuitry by which gustatory stimuli engage opioid receptor-dependent analgesia is unknown. Experiments proposed in this application will close this critical gap. My preliminary neuroanatomical findings in neonatal rats indicate that intraoral sucrose elicits increased neural activity in brainstem gustatory neurons that project directly to antinociceptive sites known to be involved in opiate receptor-dependent analgesia. Experiments in this proposal will confirm and extend these preliminary observations, and test the role of these candidate pathways in producing taste analgesia. Management of pain in neonates is problematic and pain processing in neonates is poorly understood. The proposed research will increase our understanding of, and ability to manage, neonatal pain. The overarching goal of this proposal is to elucidate the neural substrate of opiate receptor-mediated taste analgesia, a clinically significant phenomenon in human infants that occurs in response to gustatory stimulation produced by mother's milk during nursing. However, the neural substrate mediating taste analgesia is unknown. Using neonatal rats, experiments proposed in this application will close this critical gap, thereby increasing our understanding of, and ability to manage, neonatal pain.